Information

Solid-State Chemistry of Drugs - Table of Contents

PART 1: INTRODUCTION TO THE SOLID-STATE CHEMISTRY OF DRUGS

Chapter 1: Drugs as Molecular Solids
Role of solid-state technology in the pharmaceutical industry --The crystalline state: basic concepts -- A given substance can crystallize in different ways concept -- Properties that affect pharmaceutical behavior -- How crystals form -- Properties of amorphous solids -- Moisture uptake by solids -- Lyophilized powders -- Patents on various crystal forms -- Solid-state reactions of drugs -- Stability testing -- Summary -- References

PART 2: METHODS OF ANALYSIS

Chapter 2: X-Ray Crystallography
Introduction to x-ray crystallography -- Crystals -- Determination of the crystal structure -- Crystal-packing drawings -- Thermal parameters and molecular mobility -- References

Chapter 3: The X-Ray Powder Diffraction Method
Instruments for powder diffraction measurements -- Powder diffraction using synchrotron radiation -- The Hanawalt system -- Comparing x-ray powder data -- variable temperature and atmosphere studies -- Quantitative analysis of mixtures -- References

Chapter 4: Microscopy
Birefringence -- Interfacial angles -- Particle size measurements by microscopy -- Thermal microscopy -- Microscopy in freeze drying -- Scanning electron microscopy, tunneling microscopy, and atomic force microscopy -- References

Chapter 5: Thermal Methods of Analysis
Thermogravimetric Analysis (TGA) -- Differential Scanning Calorimetry (DSC) -- Calorimetry -- References

Chapter 6: Dissolution Testing
Testing -- Mechanism -- Dissolution apparatus -- Intrinsic dissolution testing -- Accuracy and interpretation -- Conclusions -- References

Chapter 7: Particle-Size Analysis
Methods for particle-size analysis -- Surface-area analysis -- Analysis of particles in metered dose inhalers -- Particle-size eduction -- References

Chapter 8: Infrared Spectroscopy of Solids
Infrared spectra of polymorphs -- Infrared spectra of solvates -- Analysis of mixtures by infrared spectroscopy -- References

Chapter 9: Solid-State NMR Spectroscopy
An overview of solid-state 13C CP/MAS NMR spectroscopy -- Solid-state NMR studies of pharmaceuticals -- Phase identification in dosage forms -- Other basic solid-state NMR experiments useful for pharmaceutical analysis -- Summary -- References

PART 3: POLYMORPHS, SOLVATES, AND AMORPHOUS FORMS

Chapter 10: Polymorphs
Classic examples of polymorphism -- Conformational and configurational polymorphism -- Sulfonamides -- Steroids -- Barbiturates -- Other drugs -- Carbohydrates -- Polymorphs of antibiotics -- Polymorphism and chemical stability -- Polymorphism and bioavailability -- Polymorphism and its pharmaceutical application -- References

Chapter 11: Hydrates and Solvates
Hydrates -- Conditions under which hydrates may form -- Formation of hydrates in air: stability of hydrates at different relative humidities -- Deliquescence and efflorescence -- Factors governing the formation of solvates in mixed solvents -- Stability of organic solvates in air -- Summary -- References

Chapter 12: Amorphous Solids
Properties of amorphous forms -- References

PART 4: PHYSICAL TRANSFORMATIONS OF CRYSTALLINE MATERIAL

Chapter 13: Polymorphic Interconversions
Interconversion of polymorphs in the solid state -- The induction of phase transformations by stresses -- Polymorphic transformations of pharmaceuticals -- Solution-mediated phase transformations of drugs -- References

Chapter 14: Loss of Solvent of Crystallization
Review of desolvation reactions -- The mechanism of desolvation reactions -- Desolvated solvates -- Summary -- References

PART 5: CHEMICAL TRANSFORMATION IN THE SOLID STATE

Chapter 15: Theoretical Analysis of Solid-State Chemical Reactions
Criteria for solid-state reactions -- Steps in a solid-state reaction -- Molecular mobility -- The topochemical postulate -- References

Chapter 16: Oxidation Reactions
Oxidations of rubrene and tetramethylrubrene -- Ozonolysis of stilbenes -- Reactions of free radicals with oxygen -- Oxidation of Vitamin A -- Oxidation of Vitamin C (ascorbic acid) in tablets -- Oxidation of Vitamin D2 -- Oxidation of reserpine -- Oxidation of polyene antibiotics -- Photooxidation of dyes used in coating tablets -- Oxidation reactions preceded by loss of solvent -- Oxidation of dialuric acid monohydrate: the importance of moisture in accelerating solid-state reactions -- Study of the solid-state oxidation of pharmaceuticals containing olefinic functionalities using microcalorimetry -- Summary -- References

Chapter 17: Additions of Gases: Solid-State Hydrolyses
Reactions of crystals with ammonia gas -- Rates of reaction of crystalline carboxylic acids with ammonia gas -- Reactions of solids with Cl 2 or Br 2-- Solid-state hydrolyses -- Summary -- References

Chapter 18: Gas-Producing Decomposition Reactions
Solid-state dehydration of hydroxyl compounds -- Solid-state decarboxylation reactions -- Decomposition of explosives -- Summary -- References

Chapter 19: Photochemical Reactions
Cinnamic acids, styrylthiophenes, and dienes: the topochemical postulate -- Anthracenes, pyrones, and oxazindones: exceptions to the topochemical postulate -- Quinones -- Indigo: the role of molecular conformation -- Polymerizations -- Dimerizations of pyrones -- Nucleic acids -- Photochemistry and mobility in amorphous solids -- Effect of ionizing radiation on crystals of biologically important compounds -- Drugs and natural products -- Summary -- References

Chapter 20: Thermal Reactions
Rearrangement reactions --Thermal retro-cycloaddition reactions -- Drugs and other compounds of biological interest -- Studies using calorimetry -- Summary -- References

Chapter 21: Reaction Kinetics
Equations for kinetic analysis of solid state reactions -- Examples of solid-state kinetic studies -- Summary -- References

Chapter 22: Miscellaneous Topics
Role of defects in solid-state reactions -- Solid-state reactions -- Cystallization -- Atomic Force Microscopy (AFM) -- Prediction of crystal structures and polymorphs -- Particle design and the physics of tablet compaction -- Solid-state stability of protein pharmaceuticals -- Mobility of solids -- Mobility and reactivity of solids -- Regulatory aspects of the solid-state chemistry of drugs -- Conclusion -- References